PDBsum entry 2bye

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protein links
Lipase PDB id
Protein chain
110 a.a.
PDB id:
Name: Lipase
Title: Nmr solution structure of phospholipasE C epsilon ra 1 domain
Structure: PhospholipasE C, epsilon 1. Chain: a. Fragment: ra1 domain, residues 2006-2114. Synonym: phospholipasE C epsilon. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: T.D.Bunney,R.Harris,N.L.Gandarillas,M.B.Josephs,S.M.Roe, H.F.Paterson,F.Rodrigues-Lima,D.Esposito,P.Gieschik, L.H.Pearl,P.C.Driscoll,M.Katan
Key ref:
T.D.Bunney et al. (2006). Structural and mechanistic insights into ras association domains of phospholipase C epsilon. Mol Cell, 21, 495-507. PubMed id: 16483931 DOI: 10.1016/j.molcel.2006.01.008
01-Aug-05     Release date:   22-Feb-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9P212  (PLCE1_HUMAN) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1
2302 a.a.
110 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Phosphoinositide phospholipase C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

myo-Inositol Phosphate Metabolism
      Reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
+ H(2)O
= 1D-myo-inositol 1,4,5-trisphosphate
+ diacylglycerol
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     intracellular signal transduction   1 term 


DOI no: 10.1016/j.molcel.2006.01.008 Mol Cell 21:495-507 (2006)
PubMed id: 16483931  
Structural and mechanistic insights into ras association domains of phospholipase C epsilon.
T.D.Bunney, R.Harris, N.L.Gandarillas, M.B.Josephs, S.M.Roe, S.C.Sorli, H.F.Paterson, F.Rodrigues-Lima, D.Esposito, C.P.Ponting, P.Gierschik, L.H.Pearl, P.C.Driscoll, M.Katan.
Ras proteins signal to a number of distinct pathways by interacting with diverse effectors. Studies of ras/effector interactions have focused on three classes, Raf kinases, ral guanylnucleotide-exchange factors, and phosphatidylinositol-3-kinases. Here we describe ras interactions with another effector, the recently identified phospholipase C epsilon (PLCvarepsilon). We solved structures of PLCvarepsilon RA domains (RA1 and RA2) by NMR and the structure of the RA2/ras complex by X-ray crystallography. Although the similarity between ubiquitin-like folds of RA1 and RA2 proves that they are homologs, only RA2 can bind ras. Some of the features of the RA2/ras interface are unique to PLCvarepsilon, while the ability to make contacts with both switch I and II regions of ras is shared only with phosphatidylinositol-3-kinase. Studies of PLCvarepsilon regulation suggest that, in a cellular context, the RA2 domain, in a mode specific to PLCvarepsilon, has a role in membrane targeting with further regulatory impact on PLC activity.
  Selected figure(s)  
Figure 3.
Figure 3. Structural Perspectives of the Complex between Ras and RA2
Figure 6.
Figure 6. Model of Two-Step Mechanism of PLC epsilon Translocation and Activation
  The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 21, 495-507) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23076158 J.B.Park, C.S.Lee, J.H.Jang, J.Ghim, Y.J.Kim, S.You, D.Hwang, P.G.Suh, and S.H.Ryu (2012).
Phospholipase signalling networks in cancer.
  Nat Rev Cancer, 12, 782-792.  
20949621 L.Gremer, T.Merbitz-Zahradnik, R.Dvorsky, I.C.Cirstea, C.P.Kratz, M.Zenker, A.Wittinghofer, and M.R.Ahmadian (2011).
Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders.
  Hum Mutat, 32, 33-43.  
21512128 R.Ghai, M.Mobli, S.J.Norwood, A.Bugarcic, R.D.Teasdale, G.F.King, and B.M.Collins (2011).
Phox homology band 4.1/ezrin/radixin/moesin-like proteins function as molecular scaffolds that interact with cargo receptors and Ras GTPases.
  Proc Natl Acad Sci U S A, 108, 7763-7768.
PDB code: 3lui
20870410 T.D.Bunney, and M.Katan (2011).
PLC regulation: emerging pictures for molecular mechanisms.
  Trends Biochem Sci, 36, 88-96.  
20553968 K.Fukami, S.Inanobe, K.Kanemaru, and Y.Nakamura (2010).
Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance.
  Prog Lipid Res, 49, 429-437.  
20729853 L.D.Wang, F.Y.Zhou, X.M.Li, L.D.Sun, X.Song, Y.Jin, J.M.Li, G.Q.Kong, H.Qi, J.Cui, L.Q.Zhang, J.Z.Yang, J.L.Li, X.C.Li, J.L.Ren, Z.C.Liu, W.J.Gao, L.Yuan, W.Wei, Y.R.Zhang, W.P.Wang, I.Sheyhidin, F.Li, B.P.Chen, S.W.Ren, B.Liu, D.Li, J.W.Ku, Z.M.Fan, S.L.Zhou, Z.G.Guo, X.K.Zhao, N.Liu, Y.H.Ai, F.F.Shen, W.Y.Cui, S.Song, T.Guo, J.Huang, C.Yuan, J.Huang, Y.Wu, W.B.Yue, C.W.Feng, H.L.Li, Y.Wang, J.Y.Tian, Y.Lu, Y.Yuan, W.L.Zhu, M.Liu, W.J.Fu, X.Yang, H.J.Wang, S.L.Han, J.Chen, M.Han, H.Y.Wang, P.Zhang, X.M.Li, J.C.Dong, G.L.Xing, R.Wang, M.Guo, Z.W.Chang, H.L.Liu, L.Guo, Z.Q.Yuan, H.Liu, Q.Lu, L.Q.Yang, F.G.Zhu, X.F.Yang, X.S.Feng, Z.Wang, Y.Li, S.G.Gao, Q.Qige, L.T.Bai, W.J.Yang, G.Y.Lei, Z.Y.Shen, L.Q.Chen, E.M.Li, L.Y.Xu, Z.Y.Wu, W.K.Cao, J.P.Wang, Z.Q.Bao, J.L.Chen, G.C.Ding, X.Zhuang, Y.F.Zhou, H.F.Zheng, Z.Zhang, X.B.Zuo, Z.M.Dong, D.M.Fan, X.He, and J.Wang (2010).
Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.
  Nat Genet, 42, 759-763.  
19645719 E.Yaman, R.Gasper, C.Koerner, A.Wittinghofer, and U.H.Tazebay (2009).
RasGEF1A and RasGEF1B are guanine nucleotide exchange factors that discriminate between Rap GTP-binding proteins and mediate Rap2-specific nucleotide exchange.
  FEBS J, 276, 4607-4616.  
19394299 T.D.Bunney, O.Opaleye, S.M.Roe, P.Vatter, R.W.Baxendale, C.Walliser, K.L.Everett, M.B.Josephs, C.Christow, F.Rodrigues-Lima, P.Gierschik, L.H.Pearl, and M.Katan (2009).
Structural insights into formation of an active signaling complex between Rac and phospholipase C gamma 2.
  Mol Cell, 34, 223-233.
PDB codes: 2w2t 2w2v 2w2w 2w2x
  19033212 T.K.Harden, S.N.Hicks, and J.Sondek (2009).
Phospholipase C isozymes as effectors of Ras superfamily GTPases.
  J Lipid Res, 50, S243-S248.  
18596699 B.Stieglitz, C.Bee, D.Schwarz, O.Yildiz, A.Moshnikova, A.Khokhlatchev, and C.Herrmann (2008).
Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II.
  EMBO J, 27, 1995-2005.
PDB code: 3ddc
19096503 C.Kiel, D.Aydin, and L.Serrano (2008).
Association rate constants of ras-effector interactions are evolutionarily conserved.
  PLoS Comput Biol, 4, e1000245.  
18728011 C.Walliser, M.Retlich, R.Harris, K.L.Everett, M.B.Josephs, P.Vatter, D.Esposito, P.C.Driscoll, M.Katan, P.Gierschik, and T.D.Bunney (2008).
Rac Regulates Its Effector Phospholipase C{gamma}2 through Interaction with a Split Pleckstrin Homology Domain.
  J Biol Chem, 283, 30351-30362.
PDB code: 2k2j
18765661 J.P.Seifert, Y.Zhou, S.N.Hicks, J.Sondek, and T.K.Harden (2008).
Dual Activation of Phospholipase C-{epsilon} by Rho and Ras GTPases.
  J Biol Chem, 283, 29690-29698.  
18354782 L.E.Goldfinger (2008).
Choose your own path: specificity in Ras GTPase signaling.
  Mol Biosyst, 4, 293-299.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
17998205 S.Yun, A.Möller, S.K.Chae, W.P.Hong, Y.J.Bae, D.D.Bowtell, S.H.Ryu, and P.G.Suh (2008).
Siah proteins induce the epidermal growth factor-dependent degradation of phospholipase Cepsilon.
  J Biol Chem, 283, 1034-1042.  
17956867 S.Yun, W.P.Hong, J.H.Choi, K.S.Yi, S.K.Chae, S.H.Ryu, and P.G.Suh (2008).
Phospholipase C-epsilon augments epidermal growth factor-dependent cell growth by inhibiting epidermal growth factor receptor down-regulation.
  J Biol Chem, 283, 341-349.  
18623072 Z.Gáspári, G.Pál, and A.Perczel (2008).
A redesigned genetic code for selective labeling in protein NMR.
  Bioessays, 30, 772-780.  
17599936 C.Kiel, and L.Serrano (2007).
Prediction of Ras-effector interactions using position energy matrices.
  Bioinformatics, 23, 2226-2230.  
17716979 M.Miertzschke, P.Stanley, T.D.Bunney, F.Rodrigues-Lima, N.Hogg, and M.Katan (2007).
Characterization of interactions of adapter protein RAPL/Nore1B with RAP GTPases and their role in T cell migration.
  J Biol Chem, 282, 30629-30642.  
16966426 L.E.Goldfinger, C.Ptak, E.D.Jeffery, J.Shabanowitz, D.F.Hunt, and M.H.Ginsberg (2006).
RLIP76 (RalBP1) is an R-Ras effector that mediates adhesion-dependent Rac activation and cell migration.
  J Cell Biol, 174, 877-888.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.